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BACKGROUND: In the Netherlands, prenatal screening for trisomy 21 in the first trimester of pregnancy for singletons is conducted through a combined test based on maternal age, nuchal translucency measurement and maternal serum free beta-hCG and PAPP-A. In our clinic risk calculations in twins are currently based on the NT of both fetuses instead of the combined test. In this study we looked at differences in early first-trimester free beta-hCG and PAPP-A between mono- and dichorionic twins. METHODS: A total of 202 twin pregnant women participated in the study and agreed to donate first-trimester serum for research. RESULTS: The data of 200 twins with normal outcome were used for setting up reference values for free beta-hCG and PAPP-A. Trisomy 21 was identified in the two remaining pregnancies. The overall median weight-corrected MoM was 1.99 for free beta-hCG, and 2.14 for PAPP-A in all twins. Monochorionic twins have a significantly lower free beta-hCG weight-corrected MoM (1.53 vs 2.11; Mann-Whitney U, p = 0.002) and a significantly lower PAPP-A weight-corrected MoM (1.59 vs 2.40; Mann-Whitney U, p = 0.003) compared to dichorionic. CONCLUSION: This study strengthened the need to make a distinction between mono- and dichorionic twins for the risk calculation in Down syndrome screening as biochemical markers are significantly lower in monochorionic than in dichorionic twins. Copyright (c) 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare screening performance for Down syndrome of the absolute risk (AR) method to the first trimester combined test (FCT) at different maternal ages., Methods: There was a retrospective analysis of 32,448 FCT. AR was defined as final risk divided by maternal age risk., Results: The likelihood of receiving a true prediction was comparable between both methods in all age groups. With the AR method, two extra Down syndrome cases were detected in women <30 years, three cases were missed in women ≥36 years, and the likelihood of receiving a false prediction decreased overall (OR 0.82, CI 0.77-0.87; P < 0.0001), in women aged 36-40 years (0.45, CI 0.41-0.51; P < 0.0001), in women aged 41-45 years (0.18, CI 0.13-0.26; P < 0.0001) and increased in women aged ≤25 years (2.12, CI 1.52-2.96; P < 0.004)., Conclusions: The AR method results in a significant decreased likelihood of receiving a false prediction with a comparable likelihood of receiving a true prediction. Thus, fewer invasive diagnostic tests will be performed. It will take away the misunderstanding about differences in screening performance for women of different ages. This might lead to a higher uptake of first trimester screening resulting in a more efficient screening policy., (© 2013 John Wiley & Sons, Ltd.)

Objective: To evaluate the performance of the first-trimester combined test (FCT) in different maternal age groups and to discuss whether adjustments in screening policies should be made., Methods: In this retrospective study data (n = 26 274) from a fetal medicine center on FCT (maternal age, fetal NT, free β-human chorionic gonadotrophin, pregnancy-associated plasma protein-A) were studied., Results: 70.6% of cases was <36 years and 43% of the Down syndrome (DS) cases were detected in this age group. For women <36 years and advanced maternal age (AMA) women (≥36 years) detection rate (DR) and false positive rate (FPR) were 94.5% and 4.1%, and 95.8% and 13.0%, respectively (cut-off 1:200). Lowering the cut-off showed an improved balance in DR and FPR. With increasing maternal age FPR and DR increased and odds of being affected given a positive result (OAPR) decreased., Conclusion: FCT is effective in women <36 and ≥36 years. The balance between FPR and DR is more favourable in women <36 years with comparable OAPR. Although FPR increases with increasing maternal age, performance of FCT in AMA women is more effective than screening based on maternal age alone. Lowering the cut-off to 1:100 in AMA women is suggested to improve screening performance. Routinely offering diagnostic testing to AMA women as a screening policy for the detection of DS seems not reasonable., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR)., Methods: PlGF concentration was retrospectively measured in first trimester serum specimens of 23 cases of early-onset PE (<34 weeks), 26 cases of IUGR (birth weight < 5th centile) and 5 controls per case. Levels were adjusted for gestational age (GA), ethnicity and smoking to obtain multiples of the expected median (MoM). Logistic regression was used to assess PlGF, PAPP-A and maternal characteristics as potential predictors of early-onset PE and IUGR., Results: PlGF MoM levels were significantly lower in the early-onset PE group (P < 0.0001) compared with controls, but not in the IUGR group. PAPP-A MoM levels were significantly lower in the IUGR group (P < 0.01) compared with controls but not in the early-onset PE group. PlGF significantly improved the ability of systolic blood pressure at the first prenatal visit to predict early-onset PE [achieving a receiver-operating characteristics curve with area under the curve (AUC) of 0.8]. Combining systolic blood pressure at the first prenatal visit and PlGF did not significantly improve the predictive ability compared with PlGF alone (AUC = 0.83)., Conclusion: Serum PlGF is an acceptable marker in first trimester screening for early-onset PE, but a poor marker in screening for IUGR. Screening performance of serum PAPP-A is poor for both early-onset PE and IUGR., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: A disintegrin and metalloprotease 12s (ADAM12s) is a potential first trimester serum marker for fetal trisomy and adverse pregnancy outcome in singletons. In this study, ADAM12s levels in first trimester serum of uncomplicated and complicated twins were evaluated., Methods: ADAM12s was studied in maternal serum of 215 twin pregnancies, collected between 2004 and 2008. ADAM12s was measured 'blind to outcome' using AutoDelfia (PerkinElmer, Turku, Finland). As a reference, data from 2423 singletons were used., Results: The median ADAM12s level was increased in euploid twins [1.61 multiples of the median (MoM); n = 209] compared with singletons. The median ADAM12s MoM was significantly lower in monochorionic (1.36 MoM; n = 41) compared with dichorionic twins (1.67 MoM; n = 168) (Mann-Whitney U test, p = 0.005). Trisomy 21 was identified in two pregnancies. Median ADAM12s MoM in twins complicated by hypertensive disorders (1.77 MoM, n = 35) or small for gestational age fetus (1.54 MoM; n = 24) was not significantly different from uncomplicated twins (1.64 MoM; n = 134)., Conclusion: Median ADAM12s MoM in euploid twins was increased compared with singletons. Monochorionic had significantly lower median ADAM12s MoM than dichorionic twins. Median ADAM12s MoMs were not significantly different in twins complicated by hypertensive disorders or small for gestational age fetus compared with uncomplicated twins., (Copyright (c) 2010 John Wiley & Sons, Ltd.)

Objective: To evaluate marker distribution of free beta-human chorionic gonadotrophin (fbeta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in singleton pregnancies conceived by assisted reproduction techniques (ART)., Methods: In vitro fertilization (IVF) (n = 203) and intracytoplasmic sperm injection (ICSI) (n = 192) cases from a database of 14 645 first-trimester combined tests (overall study group) were selected and matched to 1164 controls for gestational age at sample date and maternal age., Results: In the IVF group and ICSI group, lnPAPP-A was lower (IVF 6.74 vs 7.08; P = 0.0001; ICSI 6.59 vs 7.07; P = 0.0001) compared with the matched controls. Lnfbeta-hCG was lower in the IVF group (3.75 vs 3.90; P = 0.005) but not significantly different in the ICSI group (3.87 vs 3.93; P = 0.27). The computed correction factors for PAPP-A and fbeta-hCG were 1.42 and 1.17 for the IVF group and 1.56 and 1.05 for the ICSI group.The false-positive rate (FPR) in the IVF and ICSI group compared with the matched controls was higher (IVF 10.3% vs 8.6% and ICSI 10.9% vs 7.5%). In the overall age-biased [maternal age significantly lower compared with all ART and control groups] study group the FPR was 6.8%., Conclusion: The increase in FPR in the ART groups can be explained by decreased PAPP-A values. Therefore, an adjustment in risk analysis for Down syndrome is suggested., (Copyright (c) 2010 John Wiley & Sons, Ltd.)

Objective: To evaluate the potential of maternal serum A Disintegrin And Metalloprotease 12-S (ADAM12s) as an additional marker for the combined test in the Dutch first-trimester national Down syndrome (DS) screening program., Methods: Serum samples were collected between 2004 and 2007 as part of the national program. A total of 218 singleton cases of trisomy 21 (DS), 62 trisomy 18 (Edwards syndrome) and 29 trisomy 13 (Patau syndrome) were identified. All cases were matched with controls for gestation, maternal weight and maternal age. The serum concentration of ADAM12s was determined 'blind' to outcome and expressed in multiples of the gestation-specific median for controls (MoM)., Results: The median ADAM12s was 1.00 MoM in controls and in the DS cases at 8, 9, 10, 11, 12, 13 weeks it was 0.45 (n = 3), 0.73 (22), 0.74 (53), 0.85 (37), 0.92 (71), 1.06 (32) MoM, respectively. The median for trisomy 18 was 0.85 MoM and for trisomy 13 0.63 MoM., Conclusion: The ADAM12s MoM values were clearly reduced in early first-trimester for all trisomies. However, the screening performance for DS did not greatly improve adding ADAM12s. ADAM12s could be an additional biochemical marker for first-trimester screening for trisomies other than DS.

Objective: To investigate whether pregnancies with small for gestational age (SGA) neonates, defined as customized birth weight below the 10th centile, are associated with altered levels of metastin in maternal plasma in the first trimester., Study Design: Maternal blood was obtained between 8 and 14 weeks of pregnancy. Levels of metastin were measured in pregnancies with (n = 31) or without SGA-neonates (n = 31), matched for gestational age at venipuncture. Measurement of beta-hCG was included to study the influence of gestational age and placental volume on plasma levels of the measured markers., Results: Metastin was significantly lower in SGA-pregnancies compared to an equal number of matched uneventful pregnancies (metastin: 1376 +/- 1317 pmol/L vs 2035 +/- 1260 pmol/L, p = 0.035; mean +/- standard deviation). beta-hCG levels were not different., Conclusion: Metastin is significantly lower in maternal plasma in the first trimester, in pregnancies with SGA-neonates. It might therefore be used in combination with other markers for risk estimation of growth impairment in the first trimester., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Objectives: The presence and detectability of placental mRNA in maternal plasma opens possibilities for the development of non-invasive prenatal diagnostic tests. In this study, we tested C21orf105, a chromosome 21-encoded, placentally expressed gene, in maternal plasma of women carrying a fetus with or without trisomy 21., Methods: Using real-time RT-PCR, we determined transcript levels of target (C21orf105) and reference (hPL) genes in first-trimester plasma samples. Plasma was obtained from first-trimester EDTA blood after two sequential centrifugation steps and stored at -70 degrees C. After RNA extraction, quantitative RT-PCR was performed using Taqman probes., Results: From the 51 samples, 43 samples were conclusive. Comparison of transcript levels of C21orf105 in both groups showed no significant differences. When expressed as ratios of hPL/C21orf105, the differences between trisomy 21 and normal pregnancies remained non-significant., Conclusions: The amount of C21orf105 mRNA in maternal plasma, although situated in the Down syndrome critical region on chromosome 21 and up regulated in trisomy 21 placentas, is not higher in women carrying a fetus with trisomy 21., ((c) 2006 John Wiley & Sons, Ltd.)